Single gene that controls jet lag identified

Scientists, led by an Indian—origin researcher, have identified a master gene responsible for sleep and wake cycles, offering hope for a drug that could help reset sleep.

The discovery of the role of this gene, called Lhx1, provides scientists with a potential therapeutic target to help night—shift workers or jet lagged travellers adjust to time differences more quickly.

The results can point to treatment strategies for sleep problems caused by a variety of disorders, researchers said.

“It’s possible that the severity of many dementias comes from sleep disturbances. If we can restore normal sleep, we can address half of the problem,” said Satchidananda Panda, associate professor at the Salk Institute for Biological Studies in US, who led the research.

Every cell in the body has a “clock” — an abundance of proteins that dip or rise rhythmically over approximately 24 hours.

The master clock responsible for establishing these cyclic circadian rhythms and keeping all the body’s cells in sync is the suprachiasmatic nucleus (SCN), a small, densely packed region of about 20,000 neurons housed in the brain’s hypothalamus.

More so than in other areas of the brain, the SCN’s neurons are in close and constant communication with one another.

This close interaction, combined with exposure to light and darkness through vision circuits, keeps this master clock in sync and allows people to stay on essentially the same schedule every day.

Exposure to light resets less than half of the SCN cells, resulting in long periods of jet lag.

In the study, researchers disrupted the light—dark cycles in mice and compared changes in the expression of thousands of genes in the SCN with other mouse tissues.

They identified 213 gene expression changes that were unique to the SCN and narrowed in on 13 of these that coded for molecules that turn on and off other genes. Of those, only one was suppressed in response to light: Lhx1.

“No one had ever imagined that Lhx1 might be so intricately involved in SCN function,” said Shubhroz Gill, a postdoctoral researcher and co—first author of the paper.

Lhx1 is known for its role in neural development: it’s so important, that mice without the gene do not survive. But this is the first time it has been identified as a master regulator of light—dark cycle genes.

By recording electrical activity in the SCN of animals with reduced amounts of the Lhx1 protein, the researchers saw that the SCN neurons weren’t in sync with one another, despite appearing rhythmic individually.

Studying a mouse version of jet lag — an 8—hour shift in their day—night cycle — the scientists found that those with little or no Lhx1 readjusted much faster to the shift than normal mice.

The research was published in the journal eLife.

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